Hot Line: Timing of dosing of blood-pressure medication makes no difference
01 Sep 2024
Two presentations yesterday helped to ‘put to bed’ the issue of optimal timing of administration of blood pressure (BP)-lowering medication.
“Whether preferential lowering of night-time BP could lower CV risk has been previously studied but with varying results,1-3” explained Professor Scott Garrison (University of Alberta - Edmonton, Canada) who presented results from the BedMed trial in the general primary-care population and the BedMed-Frail trial in nursing-home residents.
In the open-label, pragmatic BedMed trial, 3,357 Canadian primary-care patients prescribed at least one once-daily antihypertensive medication were randomised to take all antihypertensives in the morning or at bedtime. The primary outcome was major adverse CV events (all-cause death, hospitalisation/ED visit for stroke, myocardial infarction [MI]/acute coronary syndrome or congestive heart failure). The BedMed-Frail trial had a similar design except that the 776 participants were residents of Canadian continuing care wards assigned to either bedtime dosing or to usual care (predominantly morning use). Their median age was 88 years.
Over a median follow-up of 4.6 years in the BedMed trial, the primary outcome occurred in 9.7% of participants in the bedtime group and 10.3% in the morning group (adjusted hazard ratio [HR] 0.96; 95% CI 0.77–1.19; p=0.70). There were no differences in safety outcomes and all-cause hospitalisation/ED visits between the groups.
Over a median of 415 days in the BedMed-Frail trial, the primary outcome occurred in 40.6% of participants with bedtime dosing and 41.9% with usual dosing (adjusted HR 0.88; 95% CI 0.71–1.11; p=0.28), and in both groups it was mostly driven by deaths. Secondary efficacy and safety outcomes were no different, except for all-cause unplanned hospitalisation/ED visits, which favoured bedtime use (HR 0.74; 95% CI 0.57–0.96; p=0.02).
Summing up, Prof. Garrison said: “We found bedtime vs. morning administration to provide no difference in major CV events, nor in potential hypotensive, visual, cognitive or other safety events in a general population and importantly, in frail older patients who are generally excluded from trials. We can now dismiss the treatment timing as being important and advise patients to take their BP medication when they are least likely to forget.”
Professor Ricky Turgeon (University of British Columbia - Vancouver, Canada) then presented a systematic review and meta-analysis of all parallel-group trials comparing CV outcomes with night-time and morning administration. The primary endpoint was a different composite of major CV events (death from any cause, non-fatal MI, non-fatal stroke or heart failure exacerbation).
BedMed, BedMed-Frail, TIME,1 Hygia2 and MAPEC3 trials were included, with data analysed from 46,606 patients. The BedMed, BedMed-Frail and TIME trials were judged to be at overall low risk of bias using the Cochrane Risk of Bias 2 tool, while there were some bias concerns with Hygia and MAPEC, particularly regarding the randomisation process.
Across the 5 trials, the incidence of the primary endpoint was not affected by evening vs. morning dosing (HR 0.71; 95% CI 0.43–1.16).
In a sensitivity analysis, the HR was 0.94 (95% CI 0.86–1.03) in the 3 trials judged to have low bias and 0.43 (95% CI 0.26–0.72) in the two trials with bias concerns.
There was no difference in all-cause mortality for evening and morning dosing (HR 0.77; 95% CI 0.51–1.16). Similarly, all other secondary endpoints were not affected by evening vs. morning dosing, including for fractures, glaucoma events and cognitive events.
“Results from the meta-analysis provide conclusive evidence that there is no difference between evening and morning dosing. Patients should take their once-daily BP-lowering medications at whatever time best suits their preferences and circumstances,” concluded Prof. Turgeon.
References
- Mackenzie IS, et al. Lancet. 2022;400:1417–1425.
- Hermida RC, et al. Eur Heart J. 2020;41:4565–4576.
- Hermida RC, et al. Chronobiol Int. 2010;27:1629–1651.
